Additional MRC Funded Projects

 

Please find the details of the additional MRC studentship projects outlined below. You can download the full project descriptions here. Studentships are fully funded for 3.5 years.

 

Key to Institutes/Centre hosting the project:

  • CNGG: MRC Centre for Neuropsychiatric Genetics and Genomics (website).
  • DRI: MRC Dementia Research Institute (website).
  • DTP: GW4 BioMed MRC DTP.
  • IEU: MRC Integrative Epidemiology Unit (website).

 

Infection, Immunity and Repair

You can download the full project descriptions here.

 

Development of a multiplex sensing platform for accurate and rapid diagnosis of sepsis
Sepsis kills one person every few seconds. Clinical symptoms and current laboratory diagnostics do not allow definitive early diagnosis. This collaborative project aims to address this shortcoming through the development of a novel sensing platform, capable of detecting both pathogen associated and host immune markers of sepsis at point-of-care.
Supervisor: Dr Pedro Estrela.
Lead Institution: Bath.
Institute/Centre: DTP.

Structure-informed design of therapeutics and vaccines based on a Staphylococcus aureus immune evasion protein
Immune evasion protein Sbi enables human pathogen Staphylococcus aureus to escape elimination by activating the innate immune system. This project aims to gain understanding in this process by studying the supra-molecular complex formed between Sbi and complement proteins and how this can be used to design new vaccines and immunotherapies.
Supervisor: Dr Jean van den Elsen.
Lead Institution: Bath.
Institute/Centre: DTP.

Understanding the functions and therapeutic potential of the Shigella surface protein IcsA
This project aims to study, at the cellular and molecular level, the multiple functions of the Shigella surface protein IcsA during shigellosis, in order to develop its use as a vaccine antigen.
Supervisor: Dr Ariel Blocker.
Lead Institution: Bristol.
Institute/Centre: DTP.

Modelling cancer biopsy and radiotherapy in zebrafish and man
This project will utilise live imaging studies in translucent zebrafish to investigate how cancer biopsy/surgery and radiotherapy impact on the local innate and adaptive immune response and how this alters cancer progression for various cancer types.  The work will lead onto clinical studies using patient samples.
Supervisor: Professor Paul Martin.
Lead Institution: Bristol.
Institute/Centre: DTP.

MicroRNA regulation of kidney macrophage function in diabetic kidney disease
Macrophages are key to Diabetic Kidney Disease (the commonest cause of kidney failure) and also to kidney injury repair. This studentship will uncover the roles of microRNAs in specifying these macrophage phenotypes in the kidney, using state of the art techniques to study cells isolated from a mouse model and from human disease.
Supervisor: Professor Donald Fraser.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Combining synthetic biology and nanotechnology for real-time precision sensing for anti-microbial resistance detection
You will undertake a PhD in synthetic biology that uses engineered BLIP proteins as novel detection and treatment methods to tackle the growing threat of microbial resistance to antibiotics. You will target beta-lactamase enzymes, which are responsible for resistance to the most important and commonly used antibiotic class, the penicillins.
Supervisor: Dr Dafydd Jones.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Investigating the impact of metallic nanoparticles and nanotherapeutics on the brain
Metal nanoparticles are increasingly used in biomedicine but their toxic impact on biological systems remain largely unknown. This multidisciplinary project, combining cell biology and chemistry, aims to explore the effects of these nanoparticles on lysosomal function in the immune system and explore how they enter the brain and induce damage.
Supervisor: Dr Emyr Lloyd-Evans.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Role of tissue-resident monocytes (Mtr) in wound healing
Wound repair is essential for tissue health and longevity. We propose that tissue-resident monocytes (MTR), a novel immune cell subset, control this process. The GW4 BioMed student will examine this hypothesis in vitro and in vivo under the supervision of experts in immune cell migration and tissue macrophages (Cardiff) and wound biology (Bristol).
Supervisor: Professor Bernhard Moser.
Lead Institution:
 Cardiff.
Institute/Centre:
 DTP.

Innate immune recognition of needle-like structures from bacterial pathogens
This project aims to investigate, at the cellular and molecular level, the interactions of the type III secretion system (T3SS) “needle” proteins and “tip” complexes from Y. pestis and Shigella with the innate immune system in order to determine how these proteins subvert the host response to promote infection.
Supervisor: Professor Kathy Triantafilou.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Stem Cell Exosomes; a system for initiating tissue repair and regeneration in diverse disease settings
Cardiovascular progenitor cells (PCs) created hope for vascular regeneration. However, PCs’ drive effects through secretion of molecules and vesicles (exosomes), and their actions depend on the microenvironment, which is made unfavorable by the disease. The project will study exosomes as therapeutic alternative to PCs for vascular regeneration.
Supervisor: Dr Jason Webber.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Integrative multi-omic study of progression to Nonalcoholic Steatohepatitis
Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, affects ~5% of the UK population. What determines the progression to NASH is unknown and there is no approved therapy. The student will develop a powerful model to profile the pathogenesis of NASH using state-of-the-art technologies in systems biology and translational medicine.
Supervisor: Dr You Zhou.
Lead Institution: Cardiff.
Institute/Centre: DTP.

The role of chromatin modifications in immune diversification and tumorigenesis
The DNA damage response, highlighted in this year’s Nobel Prize, plays a critical role in preserving genomic integrity against cancer. Paradoxically, it also promotes mutagenesis to stimulate antibody diversity against immunodeficiency. This project aims to study the role of a new chromatin modifier on antibody diversification and cancer.
Supervisor: Dr Richard Chahwan.
Lead Institution: Exeter.
Institute/Centre: DTP.

Combatting antibiotic resistance by targeting the sensory networks that control pathogenicity
Antibiotic resistance is a major problem in the treatment of bacterial infections. Novel ways of tackling infection are urgently needed. Bacteria rely upon sensory networks to sense threats and to respond accordingly. This project aims to assess the potential of targeting these sensory networks that bacteria depend upon for their survival.
Supervisor: Dr Steven Porter.
Lead Institution: Exeter.
Institute/Centre: DTP.

Serum nitrate as a biomarker of infection in gastroenteritis patients
Patients with infective gastroenteritis show extreme increases in serum nitrate levels due to high nitric oxide synthesis. Do blood serum nitrate levels reveal the cause of acute diarrhoea in patients admitted as emergency cases to hospital, and can a novel electrochemical sensor facilitate rapid bedside measurements of nitrate?
Supervisor: Professor Paul Winyard.
Lead Institution: Exeter.
Institute/Centre: DTP.

Understanding how ABI3 contributes to the aetiology of Alzheimer’s disease
A coding variant of Abi3 promotes the development of Alzheimer’s disease. Targets identified through human genetics are more likely to lead to successful drugs and coding variants are known to highlight underlying disease mechanisms. We will use genetic models and in vivo biology to understand how Abi3 regulates Alzheimer’s disease development.
Supervisor: Professor Phil Taylor.
Lead Institution: Cardiff.
Institute/Centre: DRI.

 

 

Neuroscience and Mental Health

You can download the full project descriptions here.

 

Synaptic and circuit development in cerebral cortex in a mouse model of schizophrenia
Neurodevelopmental diseases, such as schizophrenia, occur because neuronal circuits are not wired up correctly early in life. In this project, using cutting-edge two-photon microscopy, we will investigate how loss of the schizophrenia-related DISC1 gene, impairs the synaptic processes that drive neuronal circuit assembly in the young brain.
Supervisor: Dr Michael Ashby.
Lead Institution: Bristol.
Institute/Centre: DTP.

Defining deregulated endolysosomal sorting in Parkinson disease
The endolysosomal network serves an essential neuroprotective role in age-related neurodegenerative disease. This project will build on our identification of an endosomal sorting complex, termed retromer-like (RETL), and how defects in RETL activity are associated with Parkinson disease and other neurological disorders.
Supervisor: Professor Peter Cullen.
Lead Institution: Bristol.
Institute/Centre: DTP.

Is the ubiquitin ligase Siah1 neuroprotective in Alzheimer’s disease?
Early features of Alzheimer’s disease include mitochondrial and synaptic dysfunction. This PhD will test the hypothesis that manipulating the interactions between mGluRs, the ubiquitination and SUMOylation pathways, and the mitochondrial GTPase Drp1 can protect neurons and may help delay or prevent the onset of dementia.
Supervisor: Professor Jeremy Henley.
Lead Institution: Bristol.
Institute/Centre: DTP.

Overnight therapy:  treating PTSD through sleep engineering 
Recollection of traumatic memories in PTSD is highly distressing and linked to suicide risk and depression. We aim to develop a non-invasive treatment for PTSD through manipulation of sleep. Negative memories can become less distressing if they are neurally reactivated during sleep. We will explore reactivation at both systems  and cellular levels.
Supervisor: Professor Penelope Lewis.
Lead Institution: Cardiff.
Institute/Centre: DTP.

Tracking dynamic genetic and environmental influences on mood in young adults through social media analysis
A fascinating finding from human genetics is that for many complex traits the balance of nature and nurture is not fixed, but can vary in response to different life stages or environments. This project will study how genetic and environmental influences on mood vary across emerging adulthood using high-resolution time course data from social media.
Supervisor: Dr Oliver Davis.
Lead Institution: Bristol.
Institute/Centre: IEU.

In vivo modelling of human microglial alterations associated with Alzheimer’s disease polygenic risk
Genetic risk factors implicate microglial function in Alzheimer’s disease (AD). Microglia will be made from induced pluripotent stem cells derived from patients with the highest polygenic risk scores for AD. Effects of genotype on cell and molecular biology will be determined in vitro and in vivo function analysed in novel mouse chimeric models.
Supervisor: Professor Julie Williams.
Lead Institution: Cardiff.
Institute/Centre: DRI.

Complement interactions with microglia and neurones as a therapeutic target in dementia
Complement, a mainstay of innate immunity, has emerged in recent years as a driver of pathology in brain inflammation and degeneration. Implicated through genetics and pathological evidence, precisely how complement damages the brain is uncertain. The project will address interactions of complement with brain cells to identify new therapies.
Supervisor: Professor Paul Morgan.
Lead Institution: Cardiff.
Institute/Centre: DRI.

Exploiting health informatics for stratification across the mood-psychosis spectrum
This project will combine emerging knowledge about the genetics of major mental illness with the unique electronic health record resource of the NHS in order to examine the impact of genetic risk on clinical factors across traditional diagnostic boundaries using the largest samples of those with schizophrenia and bipolar disorder in the world.
Supervisor: Dr James Walters.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

De-risking Prader-Willi Syndrome drug development through preclinical screening
Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder in which individuals display behavioural and psychiatric problems. Working with the Foundation for Prader-Willi Research Pre-clinical Animal Network, the aim of this project is characterise novel PWS mouse models & standardise a pre-clinical screening platform for drug candidates.
Supervisor: Professor Anthony Isles.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

Mining genomic and other -omics data for druggable targets in schizophrenia
We will identify likely novel drug targets for schizophrenia by co-expression analysis of RNA-seq data from human neuronal cell lines carrying risk mutations. Perturbations will then be compared with human embryonic and adult brain tissue over neurodevelopmental time courses to establish which pathway components are most relevant and targetable.
NOTE: To find out more about this project or to organise an interview with the supervisory team, please contact Professor Mike O’Donovan.
Supervisor: Professor Sir Mike Owen.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

Motor problems in children with chromosomal conditions associated with high rates of neurodevelopmental disorder
Motor problems have a serious impact on a child’s daily live. Yet, little is known about the causes of motor problems. Motor problems frequently co-occur with neurocognitive and psychiatric problems, but the reasons are poorly understood. These issues will be studied in a genetically homogeneous sample of children with 22q11.2 Deletion Syndrome.
Supervisor: Professor Marianne van den Bree.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

An in vitro human cell assay to investigate the effects of psychiatric risk gene CACNA1C dosage on neuronal network activity
CACNA1C is a major psychiatric risk gene, encoding a voltage-gated calcium channel protein. Its expression will be altered in human stem cell derived neuronal lines using CRISPR-based technology, and the effects on neuronal network activity monitored by microelectrode array (MEA) technology. This will create a human cell platform for drug screening.
Supervisor: Professor Adrian Harwood.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

Sparse Support Vector Machine for stratification of schizophrenia: Identifying novel biologically valid diagnostic categories to inform precision medicine
Employing Machine Learning algorithms is one way to explore the complex architecture of BIG genetic data and one such method, Support Vector Machines (SVM). The student will investigate the performance of sparse SVMs algorithm in simulated and real schizophrenia case/control data sets.
Supervisor: Professor Valentina Escott-Price.
Lead Institution: Cardiff.
Institute/Centre: CNGG.

Integration of genetic and functional data to identify drug targets and enhance risk prediction
Integrating brain expression and protein-protein interaction data with genomic data, identified a network of immune-related genes implicated in Alzheimer’s disease susceptibility. We propose to use functional data from relevant tissues to refine this network and incorporate the results into measures of genetic disease risk prediction.
Supervisor: Professor Valentina Escott-Price.
Lead Institution: Cardiff.
Institute/Centre: DRI.

 

 

Population Health

You can download the full project descriptions here.

 

Dietary patterns and the progression of type 2 diabetes
A unique opportunity for a student with strong quantitative skills to investigate the role dietary patterns in modifying the progression of type 2 diabetes, responsiveness to diabetes medication and development of diabetes complications. Findings will inform the development of individualised approaches to treatment of Type 2 diabetes.
Supervisor: Dr Laura Johnson.
Lead Institution: Bristol.
Institute/Centre: DTP.

Blood pressure changes in pregnancy: genetic determinants and maternal consequences
High pregnancy blood pressure is associated with poor outcomes in mothers and babies; whether these associations are causal is unclear. The student will have quantitative skills and will train at 2 world-leading centres, developing expertise in the use of genetic data for understanding causes and consequences of high pregnancy blood pressure.
Supervisor: Professor Deborah Lawlor.
Lead Institution: Bristol.
Institute/Centre: DTP.

Body mass index and obesity: investigating gene-environment interactions
This studentship will investigate gene environment interactions in obesity. The student will use genotype and phenotype data from world leading resources including 500,000 individuals in the UK Biobank and 20,000 from the ALSPAC cohort. The student will develop computational, bioinformatics, statistical and epidemiological skills.
Supervisor: Professor Tim Frayling.
Lead Institution: Exeter.
Institute/Centre: DTP.

Avoiding bias in medical research due to data that are Missing Not At Random (MNAR) in the Clinical Practice Research Datalink (CPRD)
A collaborative project with the Universities of Bath and Bristol using the Clinical Practice Research Datalink primary care database to develop methods of identifying and handling data that are Missing Not At Random (MNAR). The project offers an interdisciplinary environment and training in advanced epidemiology and statistical modelling.
Supervisor: Dr Alison Nightingale.
Lead Institution: Bath.
Institute/Centre: DTP.

 Investigating molecular mediation in the onset and progression of cancer
The availability of molecular measures in large epidemiological datasets offers the potential to improve understanding of cancer processes. These factors may serve as intermediates between risk factors and disease. This project will apply statistical methods for appraising causality of molecular intermediates in cancer onset and progression.
Supervisor: Professor Caroline Relton.
Lead Institution: Bristol.
Institute/Centre: IEU.

Biomarkers of health risk in DNA methylation
Associations between DNA methylation measured in peripheral tissues and future health outcomes have been observed in numerous studies. The aim of this project is to develop models of health risk using DNA methylation profiles from a variety of human cohort studies and findings reported in the DNA methylation literature.
Supervisor: Dr Matthew Suderman.
Lead Institution: Bristol.
Institute/Centre: IEU.

Approaches to data integration and visualisation in multi-omics and epidemiological data
The aim of this bioinformatics project is to apply deep neural network approaches to molecular data to (a) predict health outcomes, (b) reduce data dimensionality and (c) generate new insights into mechanisms of disease. In parallel the project will develop approaches to the visualisation of high-dimensional molecular data.
Lead Supervisor: Dr Tom Gaunt.
Lead Institution: Bristol.
Institute/Centre: IEU.

Exploring the molecular pathways underlying orofacial cleft development
Many studies have tried to identify the most important genes associated with cleft development, but much of the findings on the role of these genes is fragmented. The student will develop and analyse a valuable database and integrated pathway map of cleft genes that scientists can use to help interpret and focus research.
Lead Supervisor: Dr Gemma Sharp.
Lead Institution: Bristol.
Institute/Centre: IEU.

Codes within codes: How genetic variation influences disease through regional changes in methylation
Understanding how genes are regulated is key to unravelling the causes of disease. We can find genetic factors that explain why these regulatory elements differ between individuals, and construct causal networks that link different areas of the genome to each other, and to disease.
Lead Supervisor: Dr Gibran Hemani.
Lead Institution: Bristol.
Institute/Centre: IEU.

What lies behind the causal impact of body mass index level and change on human health? Added value from complementary study design and deep metabolomic phenotyping
This project aims to better understand how body mass index (BMI) exerts an effect on human health and disease using metabolomics in complementary study designs and through applied genetic epidemiology.
Lead Supervisor: Dr Nicholas Timpson.
Lead Institution: Bristol.
Institute/Centre: IEU.

Gene-environment interplay in the generation of health inequalities 
This project will advance understanding of gene-environment interactions in the generation of health inequalities. Combining methods from genetics and social science, it will test whether privileged environments protect against genetic susceptibility to risky health behaviours, using ‘natural experiments’ to deal with unmeasured confounding.
Lead Supervisor: Dr Stephanie von Hinke.
Lead Institution: Bristol.
Institute/Centre: DTP.

 

To find out how to apply to one of the additional MRC Studentships, please click here.

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